European Journal of Orthodontics 31 (2009) 1–11
doi:10.1093/ejo/cjn117
© The Author 2009. Published by Oxford University Press on behalf of the European Orthodontic Society.
All rights reserved. For permissions, please email: [email protected].
Abnormal mandibular growth and the condylar cartilage
Pertti Pirttiniemi*, Timo Peltomäki**, Lukas Müller** and Hans. U. Luder***
*Department of Oral Development and Orthodontics, Institute of Dentistry, University of Oulu, Finland,
**Department of Orthodontics and Pediatric Dentistry and ***Institute of Oral Biology, University of Zurich,
Switzerland
SUMMARY Deviations in the growth of the mandibular condyle can affect both the functional occlusion
and the aesthetic appearance of the face. The reasons for these growth deviations are numerous and
often entail complex sequences of malfunction at the cellular level.
The aim of this review is to summarize recent progress in the understanding of pathological alterations
occurring during childhood and adolescence that affect the temporomandibular joint (TMJ) and, hence,
result in disorders of mandibular growth. Pathological conditions taken into account are subdivided into
(1) congenital malformations with associated growth disorders, (2) primary growth disorders, and (3)
acquired diseases or trauma with associated growth disorders.
Among the congenital malformations, hemifacial microsomia (HFM) appears to be the principal syndrome
entailing severe growth disturbances, whereas growth abnormalities occurring in conjunction with other
craniofacial dysplasias seem far less prominent than could be anticipated based on their oftendisfiguring
nature. Hemimandibular hyperplasia and elongation undoubtedly constitute the most obscure conditions that
are associated with prominent, often unilateral, abnormalities of condylar, and mandibular growth. Finally,
disturbances of mandibular growth as a result of juvenile idiopathic arthritits (JIA) and condylar fractures
seem to be direct consequences of inflammatory and/or mechanical damage to the condylar cartilage.
Introduction
The size of the mandible, including the corpus, ramus, and
condyle, as well as the timing and amount of condylar growth,
vary considerably between individuals. Factors potentially
contributing to this individual variation are the extent of
masticatory action related to the consistency of the diet
(Kiliaridis et al., 1999) and, as shown recently (Van Erum
et al., 1997; Zhou et al., 2005), genetic predisposition.
Distinct from even extreme cases of individual variation,
the deviations from normality considered in this review
constitute examples of abnormal mandibular and/or condylar
growth that are related to truly pathological alterations.
Based on their aetiology and time of appearance, they
can be classified as (1) congenital malformations with
associated growth disorders, (2) primary growth disorders,
and (3) acquired diseases or trauma with associated growth
disorders.
Congenital malformations with associated growth
disorders
The most prevalent craniofacial malformation involving
mostly unilateral condylar and ramal underdevelopment, as
well as greatly variable abnormalities of the external and
middle ear, is hemifacial microsomia [HFM; (Online
Mendelian Inheritance in Man database of Johns Hopkins
University: http://www.ncbi.nlm.nih.gov/sites/entrez?db=
omim) OMIM 164210] with an estimated frequency of about
1/5000–6000 live births. Because of the similarity with the
manifestations of Goldenhar syndrome that is characterized
additionally by vertebral defects and epibulbar dermoids, the
two conditions have been combined under the term oculoauriculo-vertebral (OAV) spectrum (Gorlin et al., 2001). Its
aetiology seems to be heterogeneous. Genetic factors, in
particular chromosomal anomalies such as deletions of 5p, 6q,
8q, 18q, and 22q; duplications of 22q; and trisomies 7, 9, 18,
and 22, have been implicated with the OAV spectrum. On the
other hand, anomalies similar to those of HFM and Goldenhar
syndrome resulted from early foetal exposure to thalidomide
or retinoic acid (Gorlin et al., 2001). In fact, a HFM-like
phenotype could be reproduced using triazine, an anti-cancer
drug, in mice and thalidomide in monkeys (Poswillo, 1973).
Poswillo (1973) suggested that haemorrhages at the
anastomosis of the external carotid and stapedial artery were
responsible for the anomalies that seemed to increase in
severity with the extension of local tissue damage. However,
there is also considerable overlap in manifestations of the
OAV spectrum, the retinoic acid syndrome, and the DiGeorge
syndrome (OMIM 188400), a condition attributed to the loss
of the T-box transcription factor TBX1 due to chromosomal
deletion 22q11.2 (Botto et al., 2003; Packham and Brook,
2003). Common to all of these three entities are cono-truncal
cardiovascular defects, which led Johnston and Bronsky
(1995) to suspect that defective neural crest cell development
could be the primary cause of HFM.
The extent of temporomandibular joint (TMJ) involvement in the OAV spectrum largely determines the timing and
type of treatment (Caccamese et al., 2006). Therefore, HFM
is often classified based on the degree of TMJ dysmorphology
2
(Mulliken and Kaban, 1987). The mildest forms (Kaban
type I), such as the example shown in Figure 1a,b, appear to
be characterized by a slightly hypoplastic mandibular
condyle and thinner than normal condylar cartilage, but
fairly normal hypertrophy of the chondrocytes and
endochondral ossification (Figure 1c,d). Hence, mandibular
growth can be expected to be only slightly deficient,
justifying the recommendation to treat these cases at skeletal
maturity using conventional orthognathic procedures
(Caccamese et al., 2006). In contrast, the severe forms of
HFM (Kaban type III), such as the case illustrated in Figure 1e,f,
exhibit aplasia or severe hypoplasia of the condyle. Even if
present, these condyles seem to completely lack condylar
cartilage and endochondral ossification (Figure 1g,h).
Hence, mandibular growth on the affected side most likely
comes to an early standstill; facial asymmetry must be
assumed to worsen progressively, and early intervention
utilizing, for example, rib grafts seems indicated to avoid
secondary tilting of the maxilla.
P. PIRTTINIEMI ET AL.
Unlike the manifestations of the OAV spectrum, those
of mandibulofacial dysostosis (MFD) are always bilateral.
The prototype MFD, Treacher Collins syndrome (TCS;
mainly in Europe also known as Franceschetti-ZwahlenKlein syndrome; OMIM 154500), occurs at a frequency of
about 1/25 000–50 000 live births. Abnormalities include
underdeveloped supraorbital ridges, downward sloping of
the palpebral fissures, and hypoplasia of the zygomatic
bones, as well as of the mandibular rami and condyles
(Gorlin et al., 2001).
TCS is an autosomal dominant disorder with variable
expressivity. Although MFD can also be caused by
chromosomal abnormalities (Stevenson et al., 2007),
most individuals with TCS bear a mutation of the TCOF1
gene. However, even among carriers of such a specific
genetic defect, the phenotype varies markedly and is
sometimes so mild that the disorder may go undetected
clinically (Teber et al., 2004). TCOF1 encodes Treacle, a
nucleolar protein. When it is defective, the biogenesis of
Figure 1 Hemifacial microsomia (HFM). (a–d) A 1.5-year-old girl with marked chin deviation (a), but mild involvement of the external ear (b) associated
with HFM on the left side; (c) overview micrograph of the left condyle replaced by a costochondral graft and (d) detail of condylar cartilage marked by the
rectangle in (c); note the diameter of the condyle (c) and the thickness of the hypertrophic cartilage (HC; d) that are approximately two-thirds of the
dimensions seen in an age-matched healthy specimen; in contrast, endochondral ossification (d; arrows) is inconspicuous. (e–h) A 14-year-old girl with
marked chin deviation (e) and severe involvement of the external ear (f) due to HFM on the left side. The overview micrograph of the resected condyle (g)
and the detail of the condylar articular surface (h) marked by the rectangle in (g) reveal that the condyle is small for the age and condylar cartilage is
completely missing. (c, d, g, and h) toluidine blue; original magnifications (c and g) ×6.3 and (d and h) ×80.
ABNORMAL CONDYLAR–MANDIBULAR GROWTH
mature ribosomes in neuroepithelial and neural crest cells
is impaired, the formation and proliferation of neural crest
cells is disturbed and, finally, the number of neural crest
cells that migrate into the branchial arches is deficient
(Dixon et al., 2006).
In agreement with this pathogenetic mechanism, the
examination of a male foetus of 130 mm crown–rump
length diagnosed as having TCS revealed that at this early
pre-natal stage, the developing maxillary and zygomatic
bones were hypoplastic. As far as the mandible was
concerned, the rami and corpus were unusually short and
abnormally shaped, while condylar cartilage was missing
on one side and markedly deficient on the other side
(Behrents et al., 1977). On the other hand, clinical and
cephalometric findings from TCS patients repeatedly show
that the craniofacial skeletal pattern observed during infancy
remained fairly stable during further development (Roberts
et al., 1975; Posnick and Ruiz, 2000). In fact, longitudinal
changes in the length of the mandible reported by Roberts
et al. (1975) appear to deviate little from control values,
suggesting that the disorder of post-natal condylar growth
associated with TCS may be far less extensive than the
primary, pre-natal establishment of an abnormal skeletal
pattern.
A clinically significant entity, also involving potential
condylar growth problems, is the Pierre Robin sequence
(PRS; OMIM 261800) with a prevalence of about
1/2000–8500 live births. It is characterized by mandibular
micrognathia, cleft palate, and glossoptosis (Gorlin et al.,
2001). Although the aetiology of the disorder so far has not
been elucidated, a recent systematic analysis of several PRS
patients and the finding of a familial translocation of
chromosomes 2 and 17 in one case suggested that genetic
defects of SOX9, a gene encoding a transcription factor
that is crucial for the differentiation of chondrocytes and
chondrogenesis, could play a role in the development of
PRS (Jakobsen et al., 2007).
A first issue of ongoing debate with respect to PRS applies
to the role played by tongue interposition as the cause for
the formation of isolated palatal clefts. It has been argued
that palatal clefts result from insufficient downward–
forward displacement of the tongue due to a retroposition of
the mandible. Alternatively, development of the tongue
itself could be defective and result in insufficient
displacement of the mandible. From the analysis of mice
carrying a genetic defect predisposing to the development
of a phenotype resembling PRS, Schubert et al. (2005)
concluded that primary mandibular retrognathia, rather than
deficient growth of the tongue, was responsible for the
formation of the clefts. It should be borne in mind, however,
that downward and forward growth of the mandibular arch
prior to the fusion of the secondary palate is accounted for
by Meckel’s cartilage, rather than secondary condylar
cartilage that develops considerably later (Diewert, 1982,
1985). When considering this, the suggested aetiological
3
involvement of defects in SOX9 (Jakobsen et al., 2007)
appears quite conceivable.
A second controversial issue related to PRS is the question
as to whether catch-up mandibular growth is able to
compensate, at least in part, for the mandibular deficiency.
While Figueroa et al. (1991) supported the possibility of
catch-up growth, Laitinen and Ranta (1992), Hermann et al.
(2004), and, recently, Eriksen et al. (2006) showed that
post-natal growth of the mandible in children with PRS is
normal and comparable with that of other children with
clefts. Also, children with PRS associated with mandibular
hypodontia had smaller mandibles than subjects with PRS
and all permanent mandibular teeth, and this pattern did not
improve with further growth (Suri et al., 2006).
In addition to these relatively frequent syndromes, there
are additional, but very rare conditions affecting the size
and shape of the mandible and possibly also condylar
growth. Examples are acrofacial dysostosis 1 (OMIM
154400) or Nager syndrome, that can be associated with
condylar ankylosis (Halonen et al., 2006), and Turner
syndrome with a short mandibular body and posterior
rotation of the mandible (Peltomäki et al., 1989; RongenWesterlaken et al., 1993; Babić et al., 1997; Perkiömäki
et al., 2005). Hemifacial atrophy (OMIM 141300) or ParryRomberg syndrome may affect mandibular growth and lead
to progressive facial asymmetry (Buonaccorsi et al., 2005),
while Hallerman-Streiff syndrome (OMIM 234100) is
characterized by a narrow upper dental arch, extensive
hypodontia, and a very small, posteriorly rotated mandible,
giving the impression of a ‘bird face’ (Defraia et al., 2005).
In Silver-Russell syndrome (OMIM 180860), the mandible
as well as the maxilla are small and retrognathic. Left–
right differences in mandibular growth causing facial
asymmetries are common (Kotilainen et al., 1995). Similarly,
children with Marfan syndrome (OMIM 154700), a
connective tissue disorder resulting from mutations in the
FBN1 gene that encodes the microfibril component
fibrillin-1, often have a retrognathic maxilla and mandible
(Westling et al., 1998).
Although less common than mandibular hypoplasia,
oversized mandibles do occur in association with some
syndromes. Acromegaly is a condition of growth hormone
overproduction. When the disease becomes manifest, the
mandible enlarges rapidly and a progenic habit develops,
sometimes in combination with sleep apnoea syndrome
due to changes in the laryngeal soft tissues. Recently, an
inherited form of acromegaly due to a germ-line mutation in
the AIP gene (OMIM 605555) has been detected. As a
result, the defective aryl hydrocarbon receptor-interacting
protein leads to a predisposition for pituitary adenoma
(Georgitsi et al., 2007). In Proteus syndrome (OMIM
176920) that is characterized by striking facial abnormalities,
one of two subforms shows unilateral condylar overgrowth
causing progressive craniofacial asymmetry (Kreiborg
et al., 1991). The stimulating influence of sex chromosomes
4
on the growth of the mandible can be clearly seen in patients
with Klinefelter’s syndrome (47,XXY). In comparison with
normal control females, these individuals have larger
mandibles, in particular larger mandibular bodies, which
cause marked mandibular prognathism.
Finally, there are craniofacial malformations that do not
affect the jaws directly, but lead to indirect, presumably
compensatory, alterations of otherwise relatively normal
condylar growth. For example, in cases of craniosynostoses
such as Crouzon (OMIM 123500), Pfeiffer (OMIM 101600),
and Apert (OMIM 101200) syndromes, unusual transverse
mandibular growth may be regarded as an attempt at
adapting to the impaired expansion of the cranial vault
(Boutros et al., 2007).
In summary, disorders of mandibular and condylar growth
associated with craniofacial malformations appear far less
extensive than could be expected, when considering the
mostly markedly disfiguring conditions. Rather than
disturbed growth, the primary establishment of an aberrant
craniofacial skeletal pattern seems to account for the clinical
impression of abnormality. Obvious exceptions from this
rule are, however, severe cases of HFM, where unilaterally
deficient or completely absent condylar growth results in
progressive facial asymmetry.
Primary growth disorders
Condylar hyperactivity can be clearly identified only
when it occurs unilaterally. Bilateral symmetric
cases are very difficult to delineate against mandibular
prognathism and seem to be very rare (Obwegeser,
2001). Unilateral condylar hyperactivity typically
becomes apparent at some time during the growth period,
most often during childhood. Hence, it constitutes a true
disorder of growth (Obwegeser, 2001). The aetiology is
largely unknown. There are reports of cases where
condylar trauma during childhood later manifested itself
as hyperplastic growth (Jacobsen and Lund, 1972;
Rubenstein and Campbell, 1985). Other possible causes
taken into consideration, but so far not substantiated, are
inflammation, hypervascularization, and unspecified
genetic factors (Obwegeser, 2001).
In the literature, condylar hyperactivity is commonly
referred to as condylar hyperplasia. This term was coined
by Rushton (1944, 1946), although it did not go unnoticed
that apart from the condyle, the entire ramus and corpus of
the hemimandible on the affected side were enlarged,
resulting in gross distortion of the lower face without
significant deviation of the chin (Figure 2a). However,
unilateral condylar hyperactivity can also manifest itself in
elongation, rather than increase in volume, of the condylar
neck, ramus, and corpus, leading to facial asymmetry with
marked deviation of the chin to the unaffected side (Figure 2b).
For this form of growth anomaly, Obwegeser and Makek
(1986) introduced the term hemimandibular elongation
P. PIRTTINIEMI ET AL.
and referred to the disorder described by Rushton
(1944, 1946) as ‘hemimandibular hyperplasia’.
Considering that the entire hemimandible, rather
than only the mandibular head, is affected in cases of
unilateral condylar hyperactivity irrespective of the clinical
classification, the question arises whether the causative
disturbance really lies in the condyle. Most previous reports
on histological findings, reviewed recently by Luder (2001),
mentioned alterations of the condylar cartilage that seemed
to indicate unusually rapid growth and/or an abnormally
long duration of growth. Slootweg and Müller (1986) even
suggested a classification of condylar hyperplasia based on
the appearance of the cartilage. However, compared with
normal age-matched specimens, differences in cartilage
morphology and thickness proved rather small (Luder,
2001). Thus, given the variation in the timing of mandibular
growth (Björk, 1963), caution seems to be warranted when
drawing conclusions as to individual growth velocity based
on the appearance of the condylar cartilage.
Another structural feature observed consistently in
hyperplastic condyles is the distribution of cartilage rests in
the subchondral spongiosa. As noted by Rushton (1944),
remnants of cartilage matrix occur at abnormally large
distances from the front of the erosion. When comparing the
various forms of condylar hyperactivity, this seems to be
particularly true for cases of hemimandibular hyperplasia
that additionally reveal a conspicuous arrangement of mixed
cartilaginous-bony trabeculae lacking a clear orientation
(Figure 2c). In contrast, condyles from subjects with
hemimandibular elongation exhibited cartilage of normal
structure and thickness, subchondral cartilage rests at
normal distances from the zone of erosion, and a spongiosa
comprising well-orientated bone trabeculae (Figure 2d;
Luder, 2001).
These findings indicate that in cases of condylar
hyperactivity, the primary vascular invasion and resorption
of cartilage, that determine its thickness, are fairly normal
or at least keep pace with cartilage growth. In contrast,
remodelling of the primary spongiosa, that is responsible
for the ultimate removal of cartilage remnants and
arrangement of the bone trabeculae, may be disturbed or
unbalanced in hemimandibular hyperplasia, but normal in
hemimandibular elongation (Luder, 2001). It is, thus,
possible that distinct pathogenetic mechanisms account
for the two clinical forms of condylar hyperactivity,
although this has yet to be confirmed by additional, more
comprehensive studies.
The question as to whether condylar growth is active or
has ceased is critical for selecting the appropriate treatment
procedure. When growth is still ongoing, high condylectomy,
although controversial, is considered an option to avoid
secondary, adaptive deformation of the maxilla. On the
other hand, corrective orthopaedic surgery should be
envisaged only when condylar growth has ceased (Marchetti
et al., 2000; Obwegeser, 2001; Deleurant et al., 2008). As
ABNORMAL CONDYLAR–MANDIBULAR GROWTH
5
Figure 2 Hemimandibular hyperplasia (HH; a, c, and e) and hemimandibular elongation (HE; b, d, and f). Dental pantomographs of a 12-year-old boy
(a) and a 13-year-old girl (b); note the distortion of the entire right hemimandible associated with HH (a) and the midline deviation to the left due to HE on
the right side (b). (c–f) Overview micrographs of the condyles (c and d) resected in the subjects shown in (a) and (b) and details of the condylar cartilage
(e and f) marked by the rectangles in (c) and (d), respectively; note the arrangement of the subchondral bone trabeculae (c and d; arrows) and the front of
endochondral ossification (e and f; arrowheads). (c–f) toluidine blue; original magnifications (c and d) ×6.3 and (e and f) ×80.
the method of choice for the assessment of condylar growth
activity, planar or three-dimensional quantification of 99m
technetium methylene diphosphonate (99m Tc-MDP)
uptake using plane scintigraphy or single photon emission
computed tomography are strongly recommended (Chan
et al., 2000; Pripatnanont et al., 2005). However, it should
be borne in mind that all these methods of bone scanning,
although highly sensitive, are non-specific, that is they do
not yield any clue as to the reason for an observed asymmetry
in condylar activity (Obwegeser, 2001).
Acquired diseases or trauma with associated growth
disorders
Juvenile idiopathic arthritis (JIA) is a chronic inflammatory
disease of unknown aetiology, which is present for longer
than 6 weeks and starts before the age of 16 years (Petty
et al., 1998). It comprises seven subtypes (systemic arthritis,
rheumatoid factor-negative and -positive polyarthritis,
oligoarthritis, enthesitis-related arthritis, psoriatic arthritis,
and others) based on clinical symptoms during the first
6 months of the disease. Overall, JIA is the most common
form of arthritis in children. Its frequency is about 1–2/1000
in most populations (Saurenmann et al., 2007) with a ratio
of girls to boys of about 3:2 (Andersson Gäre et al., 1987).
The disease is characterized by variable degrees of joint
inflammation, joint destruction, and progressive disability
(Palmisani et al., 2006).
Although the aetiology of JIA is unknown, it has clear
autoimmunological characteristics. There is, however, no
evidence indicating that some specific antigen is responsible.
Rather, it is presumed that many different factors, to varying
degrees, lead to the outbreak of the disease (Sen, 2005). For
this reason, the serological demonstration of HLA-B27,
antinuclear antibodies, and rheumatoid factor are of little
prognostic value for the course of JIA (Ilowite, 2002).
Histopathologically, JIA is characterized by hypertrophic
inflammatory synovitis with cellular infiltration and
6
proliferation of blood vessels. In the chronic state of the
disease, the articular surfaces are covered by a pannus, a
tumour-like mass of inflamed granulation tissue. The
expansion of the pannus is enhanced by extensive formation
of new blood vessels and results in cartilage and joint
destruction that may occur early in the course of the disease
(Yang et al., 2002).
Reported frequencies of TMJ involvement in JIA vary
from approximately 17 to 87 per cent, probably depending
on whether all subtypes of the disease have been taken into
account and whether the diagnoses have been based on a
purely clinical, a radiological, or even a magnetic resonance
imaging (MRI) examination (Mayne and Hatch, 1969;
Rönning et al., 1974; Küseler et al., 1998; Billiau et al.,
2007). In all subtypes, one or both TMJs can be affected and
may even be the initial joints involved (Karhulahti et al.,
1990; Küseler et al., 1998; Martini et al., 2001). While
Billiau et al. (2007) claimed that condylar damage was
unrelated to JIA subtype and disease activity, severity, or
duration, Säilä et al. (2004) reported that patients reacting
positive for antinuclear antibodies more frequently exhibited
TMJ involvement than histocompatability locus antigenpositive individuals, and Pedersen et al. (2001), based on a
study using enhanced MRI, concluded that TMJ involvement
was particularly frequent in polyarticular onset JIA. Also
based on MRI, Küseler et al. (2005) found a prevalence of
26 per cent for pannus formation in the TMJ and a frequency
of 71 per cent regarding condylar erosions.
Because of its suitability to detect even small initial
destructive lesions, MRI has become the gold standard for
TMJ examinations in subjects with JIA (Figure 3). It has
even been suggested that a panographic examination is not
indicated when a MRI is obtained (Arabshahi and Cron, 2006;
Helenius et al., 2006). High-resolution ultrasonography (US)
has been proposed as an alternative to MRI, because it can
be used while the joint is functioning, thus allowing
P. PIRTTINIEMI ET AL.
assessment of disc movements (Jank et al., 2007). However,
a closer look at the publication of those authors shows that
only severe destructive TMJ changes had been investigated.
In agreement with this observation, a recent, unpublished
pilot study indicated that US is not able to detect early TMJ
arthritis before destructive alterations have occurred. These
results suggest that while US is a valuable diagnostic
imaging method for the TMJ, it cannot yet replace a MRI
investigation.
Histopathologically, JIA seems to affect the lower and
upper TMJ compartments to markedly different degrees. In
TMJs exhibiting severe radiographic alterations where
condylar replacement with costochondral grafts seemed
indicated, the entire lower joint compartments were filled
with masses of granulomatous tissue, while the upper
compartments appeared macroscopically healthy. In
contrast, condyles showed localized to total cartilage
destruction and prominent inflammatory infiltrates of the
subchondral bone marrow (Svensson et al., 2001). Evidence
regarding the pathogenesis of cartilage destruction is
available only from investigations of rheumatoid arthritis
and osteoarthritis, both of which occur in adulthood and,
therefore, do not result in growth disturbances, although
they may entail marked remodelling of articular tissues.
According to these studies (Kanyama et al., 2000; Miyamoto
et al., 2002; Gepstein et al., 2003; Goldring, 2003; Tiilikainen
et al., 2005; Malemud, 2007), inflammatory cells populating
the synovial membrane release pro-inflammatory cytokines,
chemokines, angiogenic factors, and proteinases. Among
the secreted products that appear to exert the greatest effect
on cartilage loss are interleukin-1 (IL-1) and tumour necrosis
factor a (TNFa). The most potent angiogenic factor is
vascular endothelial growth factor which plays a critical role,
because it enhances growth of the vasculature in the inflamed
synovial tissue. IL-1 stimulates chondrocytes to produce
matrix metalloproteinases (MMPs) which, in their active
Figure 3 Juvenile idiopathic arthritis (JIA). Lateral magnetic resonance views of the right temporomandibular joint affected by JIA (a) and the contralateral
healthy joint (b) of a 13-year-old girl; note the erosion of the right condyle (a; arrowhead) and the position of the intermediate zone of the articular discs (a
and b; arrows).
ABNORMAL CONDYLAR–MANDIBULAR GROWTH
forms, effectively degrade collagens and proteoglycans.
In addition, members of the aggrecanase (ADAMTS)
family, particularly ADAMTS-4 and ADAMTS-5, seem
to participate in cartilage destruction (Yoshida et al.,
2006). Interestingly, both MMPs and aggrecanases are
also involved in remodelling processes elicited by
experimental changes in dietary loading (Pirttiniemi et al.,
2004; Yu et al., 2007).
JIA involving the TMJ is associated with characteristic
facial changes, in particular a short mandibular ramus and
backward-rotated mandibular corpus, prominent antegonial
notching, and mandibular retrognathia (Rönning et al.,
1974; Björk and Skieller, 1985; Hanna et al., 1996; Mericle
et al., 1996; Kjellberg, 1998). Whereas Twilt et al. (2006)
found that in comparison with age-matched healthy
individuals, patients with JIA, regardless of their TMJ
status, exhibited retrognathia and posterior rotation of the
mandible, craniofacial alterations were reported by
Billiau et al. (2007) to be related to the presence of
radiographic condylar damage, even if this may be mild.
Notably, however, bony erosion seems to occur later in JIA
than in adult rheumatoid arthritis (Barriga et al., 1974), and
condylar resorption seems to be present for some time
before bone destruction is radiographically detectable
(Küseler et al., 1998; Twilt et al., 2006). Thus, the destruction
of condylar cartilage, irrespective of its severity, appears
to entail significant disturbances of mandibular growth. On
the other hand, recent longitudinal studies (Twilt et al.,
2007, 2008) revealed that radiographic signs of condylar
damage completely disappeared in about half and
improved in another fifth of examined patients, while they
worsened in a few subjects that exhibited particularly high
disease activity.
Abnormal position or displacement of the TMJ disc has
emerged relatively recently as a possible cause of mandibular
growth disturbances. Disc disorders are anything but rare in
childhood. While no cases of abnormal disc position could
be detected in a sample of children ranging in age from 2
months to 5 years (Paesani et al., 1999), Ribeiro et al.
(1997) observed dislocated discs in 11 per cent of children
aged from 6 to 11 years. Also, audible joint sounds, which
may be associated with disc disorders, are relatively
frequent, even in clinically healthy children. Heikinheimo
et al. (1989) reported a frequency of 25–27 per cent, while
Henrikson et al. (2000), as well as Henrikson and Nilner
(2000), noticed joint sounds, although with fluctuating
intensity, in 39 per cent of the children examined.
In an experiment using growing rabbits, the surgical
induction of unilateral anterior disc displacement resulted
in an asymmetric reduction of ramal growth and mandibular
length, before visible osteoarthrotic TMJ changes developed
(Legrell and Isberg, 1998, 1999; Legrell et al., 1999).
The authors suggested that disc dislocation per se had a
primary adverse effect on condylar growth. Supporting
these findings, Bryndahl et al. (2006) showed that
7
bilateral anterior disc displacement in a growing animal
causes significant mandibular retrognathia. As complete
maxillomandibular immobilization does not seem to affect
mandibular growth in spite of significant histological
alterations in condylar cartilage (Isacsson et al., 1993), it is
doubtful that the observed disturbances of condylar growth
resulted from a mechanical impairment of anterior condylar
excursions, which conceivably could have been caused by
the displaced disc. Alternatively, the adverse effects on
condylar growth could also have been the consequence of
an altered masticatory function (Legrell and Isberg, 1998,
1999). On the other hand, an experimental disc perforation
created in growing rabbits initially led to increased cell
proliferation in the condylar cartilage. At longer intervals
following surgery, distinct arthrotic changes, comprising
osteophytes and flattening of the condyle developed, but at
still later time points, these changes were milder, suggesting
some local adaptation to the disc perforation (Narinobou
et al., 2000).
Mandibular trauma during childhood involves the
condylar region in 36–50 per cent of subjects (Baumann
et al., 2004). Mandibular fractures are estimated to be about
twice as frequent as noticed or diagnosed, as many of them
occur during early childhood and often pass with little
discomfort. The consequences of a trauma to the condyle
depend on its location. In the case of intracapsular fractures,
the fragments are seldom severely dislocated, but there is an
increased risk for ankylosis, particularly in children younger
than 3 years of age (Baumann et al., 2004). If the fracture
affects the condylar neck and, thus, is extracapsular, the
condylar head often becomes dislocated, almost always in a
forward–medial direction.
Long-term complications of both intra- and extracapsular
fractures, such as the development of facial asymmetry or
mandibular retrognathism and anterior open bite as well as
TMJ ankylosis or painful temporomandibular disorders,
seem to be rare and, if present, mild (Kellenberger et al.,
1996; Marianowski et al., 2003). A new condyle can even
be generated and facial symmetry may thus be recovered.
An ankylosis of the TMJ as a consequence of a childhood
condylar trauma is very rare (Marianowski et al., 2003). In
a prospective study of 38 growing patients with fractures of
the condylar neck, Lund (1974) found that in a majority of
the subjects, greater than normal, compensatory growth
occurred on the affected side, and no significant facial
asymmetry developed. In the same study, a remarkable
potential for post-traumatic condylar remodelling was
noticed, which in some instances resulted in close to
complete regeneration of a new mandibular head.
This potential for remodelling is demonstrated in the case
of a 22-year-old female illustrated in Figure 4. As a
consequence of a bicycle accident, she suffered a fracture of
the left mandibular neck with forward–medial displacement
of the condyle (Figure 4a,b). Conservative functional
treatment was started only 1 week later, when she finally
8
P. PIRTTINIEMI ET AL.
Figure 4 Condylar fracture. Dental pantomographs (a and b) of a fracture of the left condyle suffered by a 22-year-old female as a consequence of a
bicycle accident. Microradiograph of the left condyle (c), overview micrograph of the left temporomandibular joint (d), and detail of condylar cartilage (e)
marked by the rectangle in (d) 2.5 months after the accident; note the old (light) and newly formed (dark) condylar bone (c), the dislocation of the condyle
relative to the mandibular fossa (d) as well as in (e) the unusual vascularization of the articular fibrous layer (arrows) and presence of hypertrophic cartilage
and endochondral ossification (arrowheads). (d and e) Toluidine blue; original magnifications (c) ×6.3, (d) ×3, and (e) ×80.
went to see an emergency doctor. Two and a half months
after the accident, she died from a cause unrelated to the first
event, and an autopsy was carried out. The dislocated condyle
exhibited conspicuous vascularized connective tissue
underneath the articular surface and hypertrophic cartilage
involved in endochondral ossification (Figure 4d,e), which
could not be expected in a normal mandibular head of a
female of this age. As a result of endochondral ossification, a
remarkable amount of new bone had apparently been formed
at the insertion of the lateral pterygoid muscle as well as at
the zenith and posterior slope of the condyle (Figure 4c). The
location of the hypertrophic cartilage and new bone formation
gave the impression that reactivated condylar growth tended
to re-establish a normal condyle–fossa relationship. Although
no final conclusion can be drawn, this conceivably could
have occurred in response to tension exerted by the stretched
capsular apparatus, to post-traumatic inflammatory processes,
or to a combination of both.
Owing to the significant progress in research techniques,
our knowledge regarding the aetiology and pathogenesis
of disorders affecting condylar cartilage has increased
considerably during the last decades. At the same time, the
diagnostic possibilities of the TMJ have improved greatly
and allow early diagnoses of initial pathological processes.
It is to be hoped that continuing efforts in basic and clinical
research will eventually shed light on the remaining obscure
forms of mandibular growth disorders and allow the design
of new strategies for their prevention and treatment.
Address for correspondence
Pertti Pirttiniemi
Department of Oral Development and Orthodontics
Institute of Dentistry
Box 5281
90014 university of Oulu
Finland
E-mail: [email protected]
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